Screening methods and kits for gastrointestinal diseases

ABSTRACT

Methods and systems for detecting occult blood and other analytes in the water of a toilet bowl release a dye reagent into the water which produces an observable signal in the presence of the blood. The dye reagent is preferably dispersed as a liquid, powder, gel, or other form which rapidly mixes and combines with the sample. Usually, automatic mechanical or electromechanical dispensing systems are used to release the dye reagent into the water.

BACKGROUND OF THE INVENTION

[0001] 1. Field of the Invention.

[0002] The present invention relates generally to medical diagnostic methods and systems. More particularly, the present invention relates to methods and systems for detecting occult blood or other analytes in the water of the bowl of a flush toilet.

[0003] Colon and rectal cancers are a leading cause of death and disability throughout the world. Early detection and treatment of both diseases can significantly increase the chances of a patient's survival. A common diagnostic test for both diseases relies on the detection of occult blood in patient feces. Occult blood detection is most commonly performed by the patient obtaining small samples of fecal matter from stool following a bowel movement, spreading those samples thinly over a specially treated substrate, allowing the substrates to dry, and sending the dried substrates to a central laboratory or a doctor's office for testing. Usually, repeat samples will be taken over several days and collected prior to sending them for laboratory evaluation.

[0004] While quite useful if performed correctly, such home diagnostic stool testing suffers from both poor compliance and incompetent performance. Most patients are quite reluctant to process stool samples, even their own. Because of this reluctance, and undoubtedly for other reasons as well, many patients are unable to properly collect the samples, apply them to the substrates, and maintain the samples in proper condition before they are sent to the testing laboratory. Because of these problems, many patients who had been advised to sample their stools never complete the home testing program, and many of those tests which are completed are compromised so that the test reliability is reduced.

[0005] To promote compliance and reduce complexity, performance of occult blood assays directly in the water bowl of a toilet has been proposed. A variety of tablets, solid phase substrates, and other diagnostic agents have been formulated, where the user can simply drop these agents into the toilet bowl after use. While theoretically increasing patient compliance, the patient can still make mistakes in adding the reagents. The addition of dried reagents and related carriers can present mixing problems which limit the accuracy of the test. Moreover, the completion of such testing requires patient compliance, which is frequently absent due to a variety of factors.

[0006] For these reasons, it would be desirable to provide improved methods, systems, and reagents for performing occult blood testing in situ in the water bowl of a flush toilet. It would be further desirable to provide such methods and systems which are also useful for detecting other analytes in an analogous manner. The methods and systems should further reduce or eliminate the level of skill required by the patient to perform the assay. It would be particularly desirable if such methods and systems were to proceed automatically each time a toilet is used for defecation or urination, either by responding to the flushing of the toilet or to the use of the toilet in other ways. Such methods and systems would desirably further provide for unambiguous results and permit easy reading of those results by the patient. At least some of these objectives will be met by the inventions described hereinbelow.

[0007] 2. Description of the Background Art.

[0008] The preparation of dried reagents which may be added to stool in a toilet to perform occult blood assays is described in U.S. Pat. No. 4,956,300. Other patents of interest include U.S. Pat. Nos. 6,271,046 B1; 6,221,678 B1; 6,186,946 B1; 5,196,167; 5,192,501; 5,081,040; 4,725,553; 4,625,160; 4,672,654; 4,541,987; 4,511,533; 4,175,923; and 2,828,377. Toilets which are capable of performing many functions, including measuring blood in urine, are predicted in “Japanese Masters Get Closer to the Toilet Nirvana,” New York Times, Oct. 8, 2002.

BRIEF SUMMARY OF THE INVENTION

[0009] According to the present invention, occult blood and other analytes symptomatic of gastrointestinal disease are detected by the addition of a dye reagent directly into the water of the bowl of a flush toilet. The dye reagent reacts with the analyte, if present, to produce an observable signal, usually a color change in the water.

[0010] In a first aspect of the present invention, the dye reagent is dispersed into the water, typically being in a liquid, gel, powder, or solid form which rapidly dissolves in the water and mixes stool sample to promote accurate and immediate results. In a second aspect of the present invention, the dye reagent is dispensed into the toilet bowl water in response to use of the toilet, such as flushing, sitting, or by the selective manual activation of a dosing unit. In the third aspect of the present invention, systems are provided for automatically dispensing the dye reagents into the toilet bowl water in response to use.

[0011] Dispersing or otherwise adding an amount of a dye reagent in the toilet bowl water according to the first aspect of the present invention requires that the reagent be in a dispersible and/or soluble form, usually being solution (liquid), gel, powder, or solid form which rapidly dissolves and/or dispenses in the toilet bowl water. Such dispersible forms generally exclude tablets, solid phase substrates, and other forms which will not rapidly mix or dissolve with the toilet bowl water and with the stool sample therein. Usually, although not necessarily, such dispersible dye reagents will be dispensed automatically in response to a use of the toilet, as will be described in more detail hereinbelow. Less preferably, however, the dispersible forms of the dye reagent may also be selectively or manually released into the toilet bowl water, where they will quickly mix and react with the stool, producing an observable signal when the analyte is present.

[0012] The automatic dispensing of a dye reagent, according to the second aspect of the present invention, will include the release of both dispersible and non-dispersible forms of the dye reagent. That is, in addition to the liquid, gel, and powder forms of the dried reagent, the present invention further comprises automatically dispensing even non-dispersible forms, such as tablets, substrates, solid phases, and the like. Such automatic release may be in response to any use of the toilet, including flushing, sitting on the seat of the toilet, electronic proximity sensing of a patient using the toilet, detection of fecal matter entering the toilet bowl water, detecting a change in water level or turbulence in the water of the toilet bowl alter any use, including vomiting, and the like. The latter relative use detection is particularly advantageous since it avoids the dispensing of reagent when the toilet is used without fecal matter entering the toilet bowl.

[0013] In all aspects of the methods of the present invention, the dye reagent may be dispensed into the water in the toilet tank, directly into the water in the toilet bowl, or as some combination of both. For example, when the dye reagent comprises both a dye and a separate oxidizer, as described in more detail below, the dye and the oxidizer may be dispersed together or separately into the water, with either or both going into the water in the toilet tank or into the water in the toilet bowl.

[0014] The methods of the present invention preferably provide for dispensing or releasing measured amounts of the dye reagent into the tank, typically in response to flushing. Usually, such dispensing comprises dropping a measured amount of a liquid, gel, or powder. In other instances, however, dispensing may comprise dissolving an amount of a solid dye reagent (or reagent component) into the tank or the bowl of the toilet.

[0015] In all instances, the presence of the dye reagent in the toilet bowl water will produce an observable signal in the presence of blood or other analyte, typically producing a color change in the presence of blood in the water of the toilet bowl. Preferably, the dye reagent will be selected and provided in an amount which produces an observable color change at a local blood concentration in the water of 0.2 ppm and above, preferably 0.1 ppm and above. Exemplary reagents comprise an oxidizer and a dye, where the oxidizer oxidizes the dye to produce a color change in the presence of a catalyst-peroxidase from blood hemoglobin. Exemplary dyes include 3,3′ 5,5′-tetramethylbenzidine, gum guaiac, potassium guaicosulfonate; phenolphthalin, 3,3′-dimethylbenzidine, o-toluidine, 4,4′-diaminobiphenyl, and the like. Exemplary oxidizers include alkali metal perborates, OXONE, hydrogen peroxide, and the like. Immunochromatographic detection employing a monoelonaldehyde conjugal with polyclonal antibodies might also be possible.

[0016] Optionally, the methods of the present invention may further comprise selectively adding a control reagent to the toilet bowl water to confirm that the system is working and optionally calibrate the system. Suitable control substances include ______.

[0017] Systems according to the third aspect of the present invention provide for automatically dispensing a dye reagent into water in a bowl of a flush toilet. The systems include a reservoir holding a dye reagent which is capable of producing an observable signal in the presence of analyte in the toilet bowl water, and a mechanism for dispensing an amount, preferably a measured amount, of the dye reagent into the water in the toilet bowl in response to a use of the toilet. The dispensing mechanism may be configured to release the dye reagent in the water in the toilet bowl, or the water in the water tank, or some combination thereof, so that the water and dye reagent are mixed in the toilet bowl. The dispensing mechanism may comprise a mechanical device which detects flushing of the toilet and/or rise of water in the toilet bowl or toilet tank and which releases a pre-measured amount of the dye reagent in response to such detection. The pre-measured amount may be in the form of a liquid, gel, powder, or optionally be in a solid form, such as a tablet, solid phase substrate, or the like. Alternatively, the dispensing mechanism may dispense dye and oxidizer separately into the water, where the dye and/or oxidizer may be in any of the forms just mentioned. The dye reagent will be selected to provide an observable signal, the presence of the analyte typically producing a color change in the water in the presence of the analyte, such as blood. In the case of blood detection, the preferred detection ranges, reagent dye systems and the like, have been set forth above. The systems of the present invention may further comprise a control substance which may be added to the toilet bowl water to produce the observable signal when added to the water in the absence of the analyte.

BRIEF DESCRIPTION OF THE DRAWINGS

[0018]FIG. 1 is a schematic illustration of a system according to the present invention comprising a dye dispensing or dispersing apparatus in the toilet tank of a toilet.

[0019]FIG. 2 is a schematic illustration of an alternative system according to the present invention wherein the dispensing or dispersing apparatus is located in the toilet bowl of the toilet.

[0020]FIG. 3 is a schematic illustration of a third embodiment of the system of the present invention comprising an electronic toilet use detector which can be arranged to control dispensing or dispersing of the dye reagents into either the toilet bowl or the toilet tank, or both.

DETAILED DESCRIPTION OF THE INVENTION

[0021] Methods and systems according to the present invention will most commonly be used to detect fecal occult blood in stool samples in the bowl of a toilet. Such tests are useful for the early detection of colon cancer, rectal cancer, and other cancers of the gastrointestinal tract. While the tests of the present invention will not be finally determinative of disease status, they will be very useful in alerting patients of the need to contact their physicians and have further testing done. In addition to the detection of fecal occult blood, the methods and systems of the present invention will also be useful to detect other analytes associated with diseases causing appearance of certain substances in gastrointestinal tract like increased level of bilirubin in certain blood disorders, porphyrins in porhyrias, specific microorganisms in gastrointestinal infections, increased fecal fat levels in pancreatic exocrine insufficiency and others. Changes in the urine chemistry may detect diabetes (increased sugar level), renal insufficiency (proteins), renal malignancies or stones (urinary blood), increased urine calcium in parathyroidism, cathecholamines in pheochromocytoma, urine free cortisol in Cushing's disease and others.

[0022] A particular advantage of the present invention is that it provides for automatic and daily screening of a patient's condition. As mentioned before, the screening will not be determinative of disease status, but will allow the patient to seek further diagnosis. For example, in the case of suspected colon or rectal cancer, subsequent screening by colonoscopy or sigmoidoscopy would likely be in order.

[0023] The dye reagents useful in the present invention may take a variety of forms. Most simply, the reagent can be in the form of a dissolvable block which is placed in the toilet bowl or toilet tank so that it is exposed to water each time the water in the bowl or tank is replenished. Upon exposure to water, a pre-determined portion of the block will dissolve and release the dye reagent into the water. Such systems are commonly available for releasing cleaning and disinfecting reagents into toilets.

[0024] Alternatively, the dye reagent may be released into the toilet bowl and/or toilet tank using a mechanical system which dispenses a pre-measured amount of the reagent in response to a use of the toilet, such as flushing, sitting, or the like. In the case of flushing, the mechanical linkage can be made directly to the handle or valve mechanism which initiates the flush, or it can be indirectly made to a response in the change of water level in the toilet bowl or tank. Such mechanical systems may release pre-measured amounts of the liquid, gel, powder, or other dispersible forms of the dry reagent. Alternatively, the mechanical systems can release single or known numbers of tablet(s) upon each use of the toilet.

[0025] The present invention can further utilize electromechanical systems where various system components can be powered or motorized to enhance response. Additionally, the electromechanical systems can have electronic sensors incorporated for detecting a variety of events suitable for controlling the release of the dye reagents. For example, sensors can sense the physical presence of a user, the positioning of the user on the toilet seat, release of fecal matter and/or urine into the toilet bowl water, or the like. Sensing these various events can be used to control the release of the dye reagent using mechanical or electromechanical release means.

[0026] Generally, in the present invention, a reagent will be added to a toilet water. A component of the reagent will react or bind with an analyte giving a characteristic and specific system change when the analyte is present. The change may be a color change or change of electric potential of toilet bowl solution specific for the analyte. Preferred dye reagent according to the present invention will comprise a dye and an oxidizer, wherein the oxidizer oxidizes the dye to produce a color released in the water in the presence of the analyte which acts as a catalyst. Exemplary dyes include 3,3′,5,5′-tetramethylbenzidine, gum guaiac, 3,3′-dimethylbenzidine, o-toluidine, 4,4′-diaminobiphen, and the like. A particularly preferred system is the combination of 3,3′,5,5′-tetramethylbenzidine and OXONE which reacts to produce blue dye in the presence of hemoglobin.

[0027] Referring now to FIG. 1, first exemplary system 10 constructed in accordance with the principles of the present invention comprises a dispenser 12 which is mountable within the tank TA of a toilet T. Dispenser 12 is positioned so that it is at least partially covered by water when the tank TA is replenished after flushing. The immersion of the dispenser 12 in water will automatically cause the release of an amount of dye reagent into the water, as indicated by the arrow. The release can be by simple dissolution, by mechanical release (e.g. opening and closing of a float valve or similar mechanical mechanism), by electronic sensing of the water level and a motorized or other powered release of dye from the dispenser 12, and the like. The released dye reagent will remain in the water in the toilet tank until the toilet is next flushed, when the water will enter the toilet bowl B, where it will remain until the use of the toilet by a patient.

[0028] An alternative system 20 as shown in FIG. 2, relies on a dispenser 22 present in the bowl B of the toilet T. The dispenser 22 may take generally the same forms as described above with respect to sensor 12 in FIG. 1, except that the release will be in response to changes in water level within the toilet bowl B.

[0029] Additional systems 30 according to the present invention are illustrated in FIG. 3. Such systems 30 will comprise an electronic controller 32 which controls operation of a first dispenser 34 located in the toilet bowl B and/or a second dispenser 36 located in the toilet tank TA. New electronic control 32 may comprise one or more sensors which detect a toilet use, such as a water level change, sitting on the seat of the toilet, proximity of the patient to the toilet, the presence of fecal matter and/or urine in the water of the toilet bowl, or the like. In response to one or more of these sensed conditions, the control may cause the first dispenser 34 and/or the second dispenser 36 to release one or more components of the dye reagent into the water in the bowl and/or tank, respectively.

[0030] The invention has been described above in conjunction with particular embodiments. One skilled in the art, however, will appreciate that there are many alternatives, modifications, and variations of the embodiments which will fall within the scope of the claims below. The present invention is intended to embrace all such alternatives, modifications, and variations within these claims. 

What is claimed is:
 1. A method for detecting an analyte in water in a bowl of a flush toilet, said method comprising: dispersing an amount of a dye reagent in the water, wherein the dye reagent produces an observable signal in the presence of the analyte.
 2. A method as in claim 1, wherein the dispersible dye reagent is dispersed automatically in response to a use of the toilet.
 3. A method as in claim 2, wherein the dye reagent is dispersed in response to a flushing of the toilet.
 4. A method as in claim 2, wherein the dye reagent is dispersed in response to sitting on a seat of the toilet.
 5. A method as in claim 1, wherein the dye and the oxidizer are dispersed separately into the water.
 6. A method as in claim 1, wherein the dye and the oxidizer are maintained and dispersed together into the water.
 7. A method as in claim 1, wherein dispersing comprises releasing the dye reagent into the water in a water tank of the toilet, wherein the water and dye reagent are mixed as the water flows into the toilet bowl after flushing the toilet.
 8. A method as in claim 7, wherein releasing comprises dropping a measured amount of the dye reagent into the tank in response to flushing the toilet.
 9. A method as in claim 8, wherein the measured amount comprises a liquid.
 10. A method as in claim 8, wherein the measured amount comprises a gel
 11. A method as in claim 8, wherein the measured amount comprises a powder.
 12. A method as in claim 7, wherein releasing comprises dissolving an amount of solid dye reagent disposed in the tank.
 13. A method as in claim 1, wherein dispersing comprises releasing the dye reagent directly into the water in the bowl of the toilet.
 14. A method as in claim 13, wherein releasing comprises dropping a measured amount of the dye reagent into the bowl in response to flushing the toilet.
 15. A method as in claim 14, wherein the measured amount comprises a liquid.
 16. A method as in claim 14, wherein the measured amount comprises a gel.
 17. A method as in claim 14, wherein the measured amount comprises a powder.
 18. A method as in claim 13, wherein releasing comprises dissolving an amount of solid dye reagent disposed in the toilet bowl.
 19. A method as in claim 1, wherein the dye reagent produces a color change in the water in the presence of the analyte.
 20. A method as in claim 19, wherein the dye reagent produces a color change in water in the presence of blood.
 21. A method as in claim 20, wherein the dye reagent produces an observable color change at local blood concentrations in the water of 0.2 ppm and above.
 22. A method as in claim 21, wherein the dye reagent comprises an oxidizer and a dye, wherein the oxidizer oxidizes the dye to produce the color change in the presence of a peroxidase from blood hemoglobin.
 23. A method as in claim 22, wherein the dye is selected from the group consisting of 3,3′,5,5′-tetramethylbenzidine, gum guaiac, potassium guaicosulfonate; phenolphthalin, 3,3′-dimethylbenzidine, o-toluidine, 4,4′-diaminobiphenyl, and the oxidizer is selected from the group consisting of alkali metal perborates, OXONE, and hydrogen peroxide.
 24. A method as in claim 1, further comprising adding an analyte-containing control substance into the water to confirm that the observable signal is produced.
 25. A method for detecting an analyte in water in a bowl of a flush toilet, said method comprising: automatically dispensing a dye reagent into the water in response to a use of the toilet, wherein the dye reagent produces an observable signal in the presence of the analyte.
 26. A method as in claim 25, wherein dispensing comprises dispersing the dye reagent into the water so that the reaction occurs in an aqueous phase.
 27. A method as in claim 25, wherein dispensing comprises releasing a solid phase into the water, wherein the dye reagent is present on the solid phase and the reaction occurs on or at surface of the solid phase.
 28. A method as in claim 25, wherein automatically dispensing comprises releasing the dye reagent in response to flushing the toilet.
 29. A method as in claim 25, wherein automatically dispensing comprises releasing the dye reagent in response to sitting on a seat of the toilet.
 30. A method as in claim 25, wherein dispensing comprises releasing the dye reagent into the water, wherein the water and dye reagent are mixed as the water flows into the toilet bowl after flushing the toilet.
 31. A method as in claim 30, wherein a measured amount of a liquid is dispensed.
 32. A method as in claim 30, wherein a measured amount of a gel is dispensed.
 33. A method as in claim 30, wherein a measured amount of a powder is dispensed.
 34. A method as in claim 25, wherein automatically dispensing comprises dissolving an amount of solid dye reagent disposed in water in the tank.
 35. A method as in claim 25, wherein the dye and the oxidizer are dispensed separately into the water.
 36. A method as in claim 25, wherein the dye and the oxidizer are maintained and dispensed together into the water.
 37. A method as in claim 25, wherein the dye reagent produces a color change in the water in the presence of the analyte.
 38. A method as in claim 37, wherein the dye reagent produces a color change in the presence of blood.
 39. A method as in claim 38, wherein the dye reagent produces an observable color change at local blood concentrations in the water of 0.2 ppm and above.
 40. A method as in claim 39, wherein the dye reagent comprises an oxidizer and a dye, wherein the oxidizer oxidizes the dye to produce the color change in the presence of a peroxidase from blood hemoglobin.
 41. A method as in claim 40, wherein the dye is selected from the group consisting of 3,3′,5,5′,-tetramethylbenzidine, gum guaiac, potassium guaicosulfonate; phenolphthalin, 3,3′-dimethylbenzidine, o-toluidine, 4,4′-diaminobiphenyl, and the oxidizer is selected from the group consisting of alkali metal perborates, OXONE, and hydrogen peroxide.
 42. A method as in claim 25, further comprising adding an analyte-containing control substance to the water to produce the observable signal.
 43. A system for automatically dispensing a dye reagent into water in a bowl of a flush toilet, said system comprising: a reservoir holding a dye reagent which produces an observable signal in the presence of an analyte; and means for dispensing an amount of the dye reagent into the water in the toilet bowl in response to a use of the toilet.
 44. A system as in claim 43, wherein the dispensing means releases the dye reagent into the water in the toilet bowl or in a water tank of the toilet, wherein the water and dye reagent are mixed in the toilet bowl.
 45. A system as in claim 44, wherein dispensing means drops of a measured amount of the dye reagent into the water in response to flushing the toilet.
 46. A system as in claim 45, wherein the measured amount is a liquid.
 47. A system as in claim 45, wherein the measured amount is a gel.
 48. A system as in claim 45, wherein the measured amount is a powder.
 49. A method as in claim 44, wherein the dispensing means dissolve an amount of solid dye reagent disposed in the tank.
 50. A system as in claim 43, wherein the dispensing means dispenses the dye and the oxidizer separately into the water.
 51. A system as in claim 43, wherein the dispensing means maintains and dispenses the dye and the oxidizer together into the water.
 52. A system as in claim 43, wherein the dye reagent produces a color change in the water in the presence of the analyte.
 53. A system as in claim 44, wherein the dye reagent produces a color change in water in the presence of blood.
 54. A system as in claim 45, wherein the dye reagent produces an observable color change at local blood concentrations in the water of 0.2 ppm and above.
 55. A system as in claim 46, wherein the dye reagent comprises an oxidizer and a dye, wherein the oxidizer oxidizes the dye to produce the color change in the presence of a peroxidase from blood hemoglobin.
 56. A method as in claim 47, wherein the dye is selected from the group consisting of 3,3′,5,5′-tetramethylbenzidine, gum guaiac, potassium guaicosulfonate; phenolphthalin, 3,3′-dimethylbenzidine, o-toluidine, 4,4′-diaminobiphenyl, and the oxidizer is selected from the group consisting of alkali metal perborates, OXONE, and hydrogen peroxide. 